This mentored career development award outlines a five year training program for Dr. Gorden's transition to scientific independence in the field of Cancer Biology. He proposes to expand his scientific skills and background knowledge through a multidisciplinary program under the supervision of Dr. Lynn Matrisian Ph.D., Chair of the Department of Cancer Biology and an active principal investigator. The candidate seeks to continue an established and valuable mentorship with Dr. Matrisian and in addition has enlisted the guidance and support of an advisory committee of highly respected scientists in the institution, who will provide scientific and career advice. [unreadable] [unreadable] The Department of Cancer Biology provides an excellent environment for a mentored training program. This department incorporates expertise from a broad variety of disciplines and has extensive resources which are supplemented by the Vanderbilt Ingram Cancer Center, and the University at large. Dr. Gorden has laboratory space currently designated in a lab adjacent to his mentor. He has the full support of his clinical Division Chief and Departmental Chair to devote at least 75% of his time to his research during the award period. [unreadable] [unreadable] Dr. Gorden's goals are to gain the knowledge and ability in a mentored setting, to pursue an independent research career in the future. The research plan detailed here focuses on tumor stromal interactions and the role of matrix metalloproteinases (MMPs) in early colorectal cancer metastases to the liver. The over-arching hypothesis of this proposal is that tumor cells induce a host tissue MMP response, which in turn plays a role in dictating the biological behavior of the tumor at its site of metastasis. Preliminary data suggests that specific MMPs are important in the establishment and progression of colorectal liver metastases and may represent important targets for therapy in a comprehensive program to treat colorectal cancer. Three specific aims are proposed to investigate this broad hypothesis: 1) Determine the role of MMP-9 on establishment of colorectal metastases using orthotopic in vivo models and in vitro systems, as well as determining the cell of origin of MMP-9 in this system. 2) Examine the importance of MMP-11 for the sustained clonogenic growth of colorectal liver metastases. 3) Identify additional MMPs present in primary tumors and metastases to explore their significance to the metastatic process. To accomplish these aims, Dr. Gorden will learn and employ fundamental and advance techniques in molecular biology. It is expected that during the period of this award, that the grantee would progress towards his objective of becoming an independent scientific investigator. [unreadable] [unreadable]